Systemic lupus erythematosus (SLE) is a serious, chronic disease characterized by familial aggregation suggesting a strong genetic component. Indeed, eleven genetic linkages have been established (lod>3.3 or p<0.00002), demonstrating the complexity of the genetics of SLE. Most of these linkages are race specific. The unique history and population characteristics of Puerto Rico, with genetic admixture and geographic isolation, combine to provide an opportunity for investigating the etiology of SLE. The population of Puerto Rico experienced a bottleneck soon after Western contact when there may have been as few as 2500 founders. Subsequent episodic immigration of Europeans and Africans has resulted in a current population of 4 million composed of 18% Taino Indians, 45% European and 37% African. We will use capture-recapture methods to identify probands to determine population-based estimates of incidence and prevalence, relationship-specific recurrence rates, confirmation of birth order and other obsen/ations concerning family structure and environmental exposure of SLE in Puerto Rico. We propose a genetic association study that will take advantage of the unique history and population characteristics of Puerto Rico. A genome scan using 330 standard microsatellite markers will be perform to discover markers and haplotypes associated with the SLE in the Puerto Rican population. We will confirm these initial genetic associations by using estimating association with neighboring genetic markers and work toward gene identification in this areas of genetic association. Also, we will compare evidence of association at those chromosome regions suggested to be associated with SLE in the US population with the evidence in the Puerto Rican population. This study will provide new observations concerning SLE, and perhaps, new genetic effects. In addition, this study has the potential to establish that the unique history and population characteristics of Puerto Rico can be used for genetic discovery in any phenotype and will help to build genetic studies in Puerto Rico.